Effectiveness and Safety of Adjunctive Cenobamate in People with Focal-Onset Epilepsy: Evidence from the First Interim Analysis of the BLESS Study

Abstract Introduction Despite new anti-seizure medications (ASMs) being introduced into clinical practice, about one-third of people with epilepsy do not reach seizure control. Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. In randomized controlled trials, adjunctive cenobamate reduced the frequency of focal seizures in people with uncontrolled epilepsy. Studies performed in real-world settings are useful to complement this evidence and better characterize the drug profile. Methods The Italian BLESS (“Cenobamate in Adults With Focal-Onset Seizures”) study is an observational cohort study aimed to evaluate the effectiveness, tolerability, and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy in the context of real-world clinical practice. The study is ongoing and conducted at 50 centers in Italy. This first interim analysis includes participants enrolled until June 2023 and with 12-week outcome data available. Results Forty participants with a median age of 36.5 (interquartile range [IQR] 26.0–47.5) years were included. The median monthly seizure frequency at baseline was 6.0 (IQR 2.5–17.3) seizures and 31 (77.5%) participants had failed four or more ASMs before cenobamate. At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1–80.3%); 22 (55.0%) participants had a ≥ 50% reduction in baseline seizure frequency and six (15.0%) reached seizure freedom. The median number of concomitant ASMs decreased from 3 (IQR 2–3) at baseline to 2 (IQR 2–3) at 12 weeks and the proportion of patients treated with > 2 concomitant ASMs decreased from 52.5% to 40.0%. Seven (17.5%) patients reported a total of 12 adverse events, 11 of which were considered adverse drug reactions to cenobamate. Conclusion In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control and a reduction of the burden of concomitant ASMs. Trial Registration Number NCT05859854 (ClinicalTrials.gov Identifier).